Abstract 14210: Phenotype, but Not Genotype, Determines Survival in Pediatric Dilated Cardiomyopathy: A Study From the NHLBI-Funded Pediatric Cardiomyopathy Registry

IntroductionSingle-gene mutations are a known cause of dilated cardiomyopathy (DCM) in children, but the strength of association between gene-mutations and disease severity is uncertain. Combining exome-sequencing with serial assessment of disease severity may improve our understanding of this genotype-phenotype relationship.HypothesisExome sequencing will identify disease-associated mutations for isolated DCM in children, and mutation carriers will have a more severe phenotype, and a worse clinical outcome than those without identifiable mutations.MethodsA longitudinal cohort study, across 14 pediatric referral centers in North America. Patients aged 0-18 with an echocardiographic diagnosis of DCM provided DNA for exome sequencing. Heart Failure (HF) symptoms, echocardiographic LV dilation and LV ejection fraction (EF) were assessed at presentation, and prospectively for up to 2 years. Endpoints of death or cardiac transplantation were recorded.Results279 DCM probands (53% female), median age 1.6 (0.4-10.4) years, were identified between 2012-2016. Median follow up time was 1.1 (0.2-4.0) years. Pathogenic mutations were identified in 19 of 37 genes evaluated, with TTN (17%), TNNT2 (11%), MYH7 (9%), RBM20 (9%) and LMNA (8%) mutations being the most common. While 17.9% of the cohort yielded an identifiable genetic cause, children >12yrs of age had the highest genetic yield, at 33% (p